CCT244747 is a CHK1 inhibitor (IC50: 7.7 nM) and also abrogates G2 checkpoint (IC50: 29 nM).

Chk1:7.7 nM

CCT244747 poorly inhibits CHK2 (IC50 >10 μM) and CDK1 (IC50 >10 μM). CCT244747 inhibits FLT3 (IC50: 600 nM) and also inhibits cellular CHK1 function with IC50s ranging from 29 nM to 170 nM for cellular G2 checkpoint abrogation (MIA, mitosis induction assay) in HT29, SW620, MiaPaCa-2, and Calu6 cell lines; the GI50s are between 0.33 and 3μM. CCT244747 (0.3 μM) inhibits SN38 and gemcitabine-induced CHK1 activity in HT29 and SW620 colon cancer cell lines and this correlates with the abrogation of cell cycle arrest, induction of DNA damage and apoptosis [2]. CCT244747 has potent activities against CHK1, RSK1, RSK2, AMPK, BRSK1, IRAK1, and TrkA, with >80% inhibition. CCT244747 (0.5-2.0 μM) increases the sensitivity of bladder and head and neck cancer cell lines (T24, RT112, and Cal27) to radiation [3]. CCT244747 (0.5 μM) overcomes genotoxic-induced S and G2 cell cycle arrest in human colon cancer cell lines. CCT244747 (10 μM) exhibits <25% inhibition of the other ion channels including hNav1.5, hKv4.3/hKChIP2, hCav1.2, hKv1.5, hKCNQ1/hminK, hHCN4 [1].

CCT244747 (100-300 mg/kg, p.o.) inhibits gemcitabine-induced pS296 CHK1 for up to 24 h in HT29 colon tumor xenografts[1]. CCT244747 (75 mg/kg, p.o.) in combination with gemcitabine has potent antitumor effects in HT29 colon tumor xenografts and Calu6 human lung cancer xenografts. CCT244747 (100 mg/kg p.o., qd7d) significantly reduces tumor burden in human tumor xenografts. CCT244747 (100 mg/kg, p.o.) exhibits radiosensitization activity in Cal27 xenografts [3]. CCT244747 (150 mg/kg p.o.) also shows antitumor activities with irinotecan in SW620 human colon tumor xenografts [2].